Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts

Robert T O'Donnell, Yunpeng Ma, Hayes C. McKnight, David Pearson, Joseph Tuscano

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH2-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm 3 had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled- HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7.

Original languageEnglish (US)
Pages (from-to)2051-2058
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume58
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Heterografts
Immunotherapy
Epitopes
Lymphoma
Appointments and Schedules
B-Lymphocytes
Neoplasms
Cell Adhesion Molecules
Nude Mice
Half-Life
Copper
Pharmacokinetics
Apoptosis
Ligands
Survival
Therapeutics

Keywords

  • Antibody
  • CD22
  • Lymphoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts. / O'Donnell, Robert T; Ma, Yunpeng; McKnight, Hayes C.; Pearson, David; Tuscano, Joseph.

In: Cancer Immunology, Immunotherapy, Vol. 58, No. 12, 12.2009, p. 2051-2058.

Research output: Contribution to journalArticle

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